Early Anakinra Treatment for COVID-19 Guided by Urokinase Plasminogen Receptor

Kyriazopoulou, E.; Poulakou, G.; Milionis, H.; Metallidis, S.; Adamis, G.; Tsiakos, K.; Fragkou, A.; Rapti, A.; Danoulari, C.; Fantoni, M.; Kalomenidis, I.; Chrysos, G.; Angheben, A.; Kainis, I.; Alexiou, Z.; Castelli, F.; Serino, F. S.; Bakakos, P.; Nicastri, E.; Tzavara, V.; Kostis, E.; Dagna, L.; Koufargyris, P.; Dimakou, K.; Tzatzagou, G.; Chini, M.; Bassetti, M.; Katrini, K.; Kotsis, V.; Tsoukalas, G.; Selmi, C.; Bliziotis, I.; Samarkos, M.; Doumas, M.; Ktena, S.; Masgala, A.; Papanikolaou, I.; Argyraki, A.; Cardellino, C. S.; Katsigianni, E.-I.; Giannitsioti, E.; Cingolani, A.; Akinosogl,

Background In a previous open-label trial, early anakinra treatment guided by elevated soluble urokinase plasminogen activator receptor (suPAR) prevented progression of COVID-19 pneumonia into respiratory failure. Methods In the SAVE-MORE multicenter trial, 594 hospitalized patients with moderate and severe COVID-19 pneumonia and plasma suPAR 6 ng/ml or more and receiving standard-of-care were 1:2 randomized to subcutaneous treatment with placebo or 100 mg anakinra once daily for 10 days. The primary endpoint was the overall clinical status of the 11-point World Health Organization ordinal Clinical Performance Scale (WHO-CPS) at day 28. The changes of the WHO-CPS and of the sequential organ failure assessment (SOFA) score were the main secondary endpoints. Results Anakinra-treated patients were distributed to lower strata of WHO-CPS by day 28 (adjusted odds ratio-OR 0.36; 95%CI 0.26-0.50; P<0.001); anakinra protected from severe disease or death (6 or more points of WHO-CPS) (OR: 0.46; P: 0.01). The median absolute decrease of WHO-CPS in the placebo and anakinra groups from baseline was 3 and 4 points respectively at day 28 (OR 0.40; P<0.0001); and 2 and 3 points at day 14 (OR 0.63; P: 0.003); the absolute decrease of SOFA score was 0 and 1 points (OR 0.63; P: 0.004). 28-day mortality decreased (Hazard ratio: 0.45; P: 0.045). Hospital stay was shorter. Conclusions Early start of anakinra treatment guided by suPAR provides 2.78 times better improvement of overall clinical status in moderate and severe COVID-19 pneumonia. (Sponsored by the Hellenic Institute for the Study of Sepsis ClinicalTrials.gov identifier, NCT04680949)